Epidemiology of dengue reported in the World Health Organization’s Western Pacific Region, 2013–2019

The global burden of dengue, an emerging and re-emerging mosquito-borne disease, increased during the 20-year period ending in 2019, with approximately 70% of cases estimated to have been in Asia. This report describes the epidemiology of dengue in the World Health Organization’s Western Pacific Region during 2013–2019 using regional surveillance data reported from indicator-based surveillance systems from countries and areas in the Region, supplemented by publicly available dengue outbreak situation reports. The total reported annual number of dengue cases in the Region increased from 430 023 in 2013 to 1 050 285 in 2019, surpassing 1 million cases for the first time in 2019. The reported case-fatality ratio ranged from 0.19% (724/376 972 in 2014 and 2030/1 050 285 in 2019) to 0.30% (1380/458 843 in 2016). The introduction or reintroduction of serotypes to specific areas caused several outbreaks and rare occurrences of local transmission in places where dengue was not previously reported. This report reinforces the increased importance of dengue surveillance systems in monitoring dengue across the Region.

where c is the total dengue notification case count in a given year and p is the population estimate for the Region in a given year. United Nations population estimate data were used for calculations. Population data for the Pitcairn Islands were not included in the United Nations population database. 12 Therefore, we used the closest population estimates based on the Pitcairn Islands' government website. In this report, an outbreak is defined as the "occurrence of cases of disease in excess of what would normally be expected in a defined community, geographical area or season". 13

RESULTS
In the Region, the total number of annual dengue cases reported increased from 430 023 cases from 22 (Fig. 2). There were challenges in calculating the CFRs for some countries due to limited reporting on dengue cases or deaths associated with dengue, or both.  Table 2).
From 2013 to 2019, large-scale outbreaks with notable increases in the number of cases were reported in multiple countries. Outbreaks were reported from the PICs every year from 2013 to 2019. There were two notable years, 2017 and 2019, when multiple outbreaks were reported across the Region, including in the PICs, with seven countries reporting outbreaks. All dengue serotypes (DENV-1, DENV-2, DENV-3 and DENV-4) previous Regional dengue epidemiology updates in 2010, 2011 and 2012, 8-10 this analysis reports data collated by the WHO Regional Office for the Western Pacific to describe the epidemiology of dengue in the Region from 2013 to 2019 using regional surveillance data. Data from 2020 to 2021 were excluded due to changes in reporting practices, population movement and people's behaviours as a result of the COVID-19 pandemic.

METHODS
Regional dengue data from 2013 to 2019 were collated from indicator-based surveillance systems from countries and areas in the Region. Information was also collected about laboratory sampling schemes and the confirmation methods used by each country and area. Data were either sent to WHO by ministries of health or collected from official websites where they were publicly available. Additional data -including serotype information, case definitions, and the numbers of clinically confirmed cases, laboratoryconfirmed cases and imported cases and deaths -were provided by Australia, Cambodia, Japan, the Republic of Korea, Malaysia, New Zealand, Pacific Island countries and areas (PICs), the Philippines, Singapore and Viet Nam. Information was reported based on the standard dengue case definitions used in each country or area ( Table 1). Missing data were supplemented by using official dengue outbreak situation reports published on ReliefWeb (https:// reliefweb.int/), manuscripts identified through PubMed using keywords ["dengue" AND "outbreak" AND "(country/ area name)"], yearly aggregated data collected from all countries and areas in the Region through International Health Regulations (2005) channels, and WHO Regional biweekly dengue reports. 11 Table 1 summarizes the dengue surveillance systems, case definitions, laboratory sampling methods and serotype data. It was not possible to compare trends between countries and areas due to the differences in surveillance methods and reporting practices. The crude regional case notification rate per 100 000 population per year was calculated using the number of cases and deaths reported to WHO and standard calculation methods: Case notification rate per 100 000 population per year = (c/p) × 100 000 and 95% confidence interval = (100 000/p) (c ± 1.96 × √c), Epidemiology of dengue in the WHO Western Pacific Region, 2013-2019 Togami et al liver enlargement and increase in haematocrit with a rapid decrease in platelet count; and (iii) severe dengue, which is characterized by severe plasma leakage, severe haemorrhage and severe organ impairment. Other countries used other case definitions ( Table 1). Some countries and areas in the Region report all identified cases of dengue, whereas others report only dengue cases at sentinel sites. In addition, some countries and areas conduct active surveillance or vector surveillance, or both ( Table 1).

Reporting by country and area
Data for dengue cases were available from 35 countries and areas during this study period, including eight with complete case and death data for all years of this study ( Table 3). Data were not available for three countries and areas: the Northern Mariana Islands, the Pitcairn Islands and Tokelau.
were reported in the Region during the review period. Concurrent infections with two serotypes were reported in some countries. While some countries reported the same predominant serotype from 2016 to 2018, others reported changes in the predominant serotype. Additionally, there were reports of the introduction of a new serotype or switch in the predominant serotype, which was subsequently followed by outbreaks. Rare cases of autochthonous transmission were reported in countries where most previously reported cases had been imported.
Laboratory sampling schemes and confirmation methods varied by country and area. Some countries in this report were using the 2009 WHO dengue case classification system: 14 (i) dengue without warning signs; (ii) dengue with warning signs that include abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy or restlessness, The data included in this figure are a subset of the data presented in Fig. 1.

Cambodia
During 2013-2019, Cambodia annually reported from 6372 to 68 597 suspected cases and from 3 to 59 deaths. The highest number of cases was reported during an outbreak in 2019 that peaked between June and August, with more than 5000 cases reported in epidemiological week 26. 15, 16 The highest number of deaths (59) was reported in 2013 (CFR: 0.34%).

American Samoa
American Samoa reported clinically confirmed cases to WHO using the 2009 WHO dengue case classification system. Laboratory confirmation is conducted to confirm outbreaks using reverse transcription polymerase chain reaction (RT-PCR) or an antigen rapid diagnostic test (NS1). In 2015, American Samoa reported 479 cases and 4 deaths (CFR: 0.84%). Outbreaks were also reported in 2017 and 2018, but the total numbers of cases are not available.

New Caledonia
New Caledonia reported cases to WHO using the 2009 WHO dengue case classification system and RT-PCR for laboratory confirmation. In 2013, New Caledonia reported 9958 cases including 4 deaths during an outbreak in which the predominant serotype was DENV-1. 39 Based on available information, an outbreak was also reported in 2014. In 2017, 4200 cases and 11 deaths were reported, with DENV-1, DENV-2 and DENV-3 detected. From November 2018 to September 2019, a dengue outbreak was declared. From 1 January to 31 December 2019, 3916 cases, 368 hospitalizations and 2 deaths were reported. Among the 316 cases with serotype information available, the predominant serotype was DENV-2. Two cases of DENV-1 and 1 case of DENV-4 were imported from French Polynesia and Indonesia, respectively. 40

Niue
Niue reported clinically confirmed cases to WHO. In Niue, 2 cases were reported in 2017. In 2018, DENV-2 was reported, but information on the number of cases was not available.

Palau
Palau reported cases to WHO using the 2009 WHO dengue case classification system and RT-PCR or an antigen rapid diagnostic test (NS1) for laboratory testing to confirm outbreaks. During 2013-2017, Palau annually reported between 9 and 737 cases and 0 to 5 deaths. Outbreaks were reported in 2016 and again in 2017, the latter comprising 440 cases and 5 deaths, with a predominant serotype of DENV-2. In 2018, 570 cases and 2 deaths were reported, and in 2019, there were Guam Guam reported clinically confirmed cases to WHO: 23 cases were reported in 2019, with no further information available.

Kiribati
Kiribati reported clinically confirmed cases to WHO using the 2009 WHO dengue case classification system. Laboratory testing to confirm outbreaks is conducted using RT-PCR or an antigen rapid diagnostic test (NS1). In Kiribati, outbreaks were reported in 2013 and 2014, and no cases were reported in 2016 and 2017. In 2018, 1899 cases and 2 deaths were reported, with DENV-2 detected.

Republic of the Marshall Islands
In the Republic of the Marshall Islands, outbreaks were reported in 2013 and 2014. In 2019, a DENV-3 outbreak was reported with at least 1395 cases of dengue-like illness, including 431 laboratory-confirmed cases and 1 death. 37 A health emergency was declared in relation to this event; internal movement restrictions were imposed between the affected and unaffected islands; and emergency medical teams were deployed to support the dengue response.

Federated States of Micronesia
The Federated States of Micronesia reported clinically confirmed cases to WHO using the 2009 WHO dengue case classification system. Laboratory methods used to confirm outbreaks include RT-PCR and an antigen rapid diagnostic test (NS1). There were 217 cases reported to WHO in 2013, associated with an outbreak of 729 suspected dengue cases and no deaths in Kosrae from September 2012 to March 2013. DENV-4 was detected from 3 specimens collected during this period; 11% (728/6600) of Kosrae residents met the case definition for suspected dengue, and almost 4% (242/6600) were hospitalized. 38 In 2018, DENV-4 was reported. In 2019, 1464 dengue cases including 1 death were reported from Yap state, and the predominant serotype was DENV-3. The dengue outbreak in 2019 coincided with a concurrent leptospirosis outbreak in Yap state, and an executive order determining a public health crisis was issued.

Vanuatu
Vanuatu reported clinically confirmed cases to WHO. In Vanuatu, 1561 cases were reported in 2014 and more than 1000 cases were reported in 2017; DENV-2 was reported in 2018.

Wallis and Futuna
Wallis and Futuna reported cases to WHO using the 2009 WHO dengue case classification system. In Wallis and Futuna, 94 cases were reported in 2013. In 2017, an outbreak was declared in November, with 222 cases and no deaths, and DENV-1 was identified from 2 samples. In 2018, 202 cases and DENV-1 were reported. In November 2019, an outbreak was declared in Wallis and Futuna, and 30 confirmed cases were reported from February to December 2019, with the predominant serotype being DENV-2. 43

DISCUSSION
Dengue continued to pose a health burden in the Region during 2013-2019, with the number of annually reported cases ranging from a little more than 430 000 to more than 1 million and with the annual number of reported deaths ranging from 724 to 2025. Outbreaks were reported from the Region every year during the study period. The introduction or reintroduction of serotypes to specific areas caused several outbreaks and rare occurrences of local transmission in places where dengue had not been previously reported. With support from countries and areas, WHO continued to share timely information during the study period through its biweekly dengue epidemiological reports for the Region 11 and conducted regional and country-specific risk assessments to inform dengue prevention and control efforts. 737 cases including 3 deaths. From December 2018 to September 2019, 160 cases were confirmed as DENV-3. Two serotypes were reported from Palau; DENV-2 was reported in 2016 and 2017, and DENV-3 was reported in 2018.

Papua New Guinea
In 2014, Papua New Guinea reported 6 cases. Further information was not available.

Samoa
Samoa reported cases to WHO using the 2009 WHO dengue case classification system and RT-PCR or an antigen rapid diagnostic test (NS1) to confirm outbreaks. In Samoa, outbreaks were reported in 2015 and 2016. In 2017, 2724 cases and 5 deaths were reported, with the predominant serotype being DENV-3. In 2018, DENV-2 was reported.

Solomon Islands
The Solomon Islands reported cases to WHO using the 2009 WHO dengue case classification system. In the Solomon Islands in 2013, 9500 cases and 8 deaths (CFR: 0.10%) were associated with an outbreak in Honiara. DENV-3 genotype I was isolated from specimens collected during this outbreak, suggesting introduction from south-east Asia after 18 years of dengue absence in the PICs. 35 In 2014, 1872 cases and 1 death (CFR: 0.05%) were reported. The introduction of DENV-2 to the Solomon Islands resulted in outbreaks in 2016 and 2017. 41,42 From September 2016 to April 2017, an outbreak of DENV-2 was reported in 9 of 10 provinces in the Solomon Islands, with 12 329 suspected cases, including 1510 cases positive by dengue rapid diagnostic test, and 16 deaths. 42 An outbreak was also reported in 2019.

Tonga
Tonga reported cases to WHO using the 2009 WHO dengue case classification system. In Tonga, 51 cases and no deaths were reported in 2014; 1559 cases and no deaths were reported in 2015; and more than 100 cases were reported in 2017.
Epidemiology of dengue in the WHO Western Pacific Region, 2013-2019 Togami et al whether the infection was locally acquired or imported. These details will also support risk assessments for and responses to events with new epidemiological patterns, such as outbreaks associated with the introduction or reintroduction of serotypes to specific areas, as well as rare occurrences of local transmission in places where it was not previously reported. Furthermore, in some settings, the capacities for surveillance, outbreak response, clinical management and diagnosis may be limited. Several approaches could fill these gaps, including strengthening laboratory capacity and laboratory networks, institutionalizing active surveillance to detect dengue cases who are self-managed and inapparent, and implementing integrated vector surveillance.
Although several countries and areas have adopted the 2009 WHO dengue case classification system, 14 there are differences in countries and areas across the Region in surveillance methodology, including whether universal or sentinel reporting is used; laboratory sampling schemes and confirmation methods; and reporting practices. These differences are a limitation of this report, indicating why comparison across countries should be avoided and comparisons within one country should be informed by the local reporting practices, which may change over time. As a result of differences in case definitions and other factors, there is likely to be underreporting and, thus, an underestimation of the true regional burden in terms of the number of cases, CFRs and incidence. 1,2 Despite these limitations, continued reporting of dengue in line with the Regional Action Plan is important to guide public health authorities in their national and subnational response efforts.
The burden of dengue, including the increased risks of dengue outbreaks, will continue amid other public health emergencies. Disaggregating data by age and sex at all levels will enable public health authorities to implement improved and targeted response measures. Additional information about cases, including their travel history and serotype, should also be routinely collected and reported. The Region's capacity to mitigate the impact of dengue can be strengthened by making a shift in its management, from a reactive, acute outbreak response to one that reduces fatalities through undertaking activities, including sustainable implementation of mosquito control measures, engaging communities to raise their awareness about the risk of dengue and to communicate The increases in reported cases and regional case incidence may be attributed to several factors. First, a true increase in dengue incidence may have occurred due to expanding urbanization and increasing population size and density, particularly in settings with increased exposure to competent dengue vectors and mosquito breeding grounds. 44 Shifts in ecological factors due to climate change, such as intensified rainy seasons and higher ambient temperatures, have expanded the geographical range of Aedes mosquitos globally during the past 50 years and led to intensified dengue transmission. 45 Second, increased international travel and trade have led to the importation of cases with different serotypes and the introduction of mosquito eggs through the importation of goods to areas where the population is susceptible and competent mosquitos exist. 44, 45 Third, reports to national health authorities likely increased due to strengthened surveillance systems and diagnostic capacities, including laboratory networks that supported confirmatory diagnosis in the PICs, as well as an emphasis on risk communication activities to improve the awareness of dengue among the public. 3 The range of CFRs may be associated with differences in case reporting, the timing of the case presentation to health-care facilities and clinical management.
The number of cases reported in 2019 was higher than in the years from 2013 to 2018, and the CFR was relatively low. This increase in 2019 included at least 14 countries and areas that reported dengue outbreaks in the Region, including large-scale outbreaks; during 2019, four countries and areas in the Asia subregion and three in the Pacific subregion reported their highest number of cases of the 7-year study. It is possible that case detection and reporting increased due to improved awareness of dengue among health-care professionals and the public because of the large outbreaks. These outbreaks may have also increased health-care-seeking behaviour, leading to fewer deaths, thereby decreasing the CFR.
Our findings show that there is a substantial burden of dengue in the Region and that it continues to increase over time. However, dengue surveillance practices throughout the Region are inconsistent and require strengthening. To inform national and regional risk assessments and actions, information is required not only on the time, place and demographics of a case, such as age and sex, but also on the DENV serotype and relevant behavioural changes, and strengthening diagnostics and case management. Enhancing collaboration and coordination within and beyond the health sector is key to carrying out these activities successfully.